| Title: |
A randomized comparison of antiretroviral therapy alone versus antiretroviral therapy with a 'kick-and-kill' approach, on measures of the HIV reservoir amongst participants with recent HIV infection: the RIVER trial |
| Authors: |
Fidler, Sarah; Stohr, Wolfgang; Pace, Matt; Dorrell, Lucy; Lever, Andrew; Pett, Sarah; Kinloch-de-Loes, Sabine; Fox, Julie; Clarke, Amanda; Nelson, Mark; Thornhill, John; Khan, Maryam; Fun, Axel; Bandara, Mikaila; Kelly, Damian; Kopycinski, Jakub; Hanke, Tomas; Yang, Hongbing; Bennett, Rachel; Johnson, Margaret; Howell, Bonnie; Barnard, Richard; Wu, Guoxin; Kaye, Steve; Wills, Mark; Babiker, Abdel; Frater, John |
| Publisher Information: |
Elsevier |
| Publication Year: |
2019 |
| Collection: |
Apollo - University of Cambridge Repository |
| Description: |
Summary Background: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing - termed ‘kick and kill’ - have been explored as a strategy towards an HIV cure. RIVER is the first randomized trial to determine the impact of ART alone versus ART plus ‘kick-and-kill’ on markers of the HIV reservoir. Methods: RIVER (Trial registration: NCT02336074) was an open-label, multicenter, 1:1 randomized controlled trial of ART-only (control) versus ART plus the histone deacetylase inhibitor vorinostat (the ‘kick’) and replication-deficient viral vector vaccines encoding conserved HIV sequences ChAdV63.HIVconsv-prime, MVA.HIVconsv-boost T-cell vaccination (the ‘kill’) (ART+V+V; intervention) in HIV-positive adults treated in recent HIV-infection. The primary endpoint was total HIV DNA in peripheral blood CD4+ T-cells at weeks 16 and 18 post-randomization. Secondary endpoints included safety, alternative measures of the HIV reservoir including quantitative viral outgrowth, HIV-specific T-cell frequencies, and CD8+ T-cell mediated viral inhibition. Findings: Between December 2015 and November 2017, 60 HIV-positive male participants were randomized (computer-based and stratified by time since diagnosis; 30 participants in each trial arm) and completed the study interventions, with no loss-to-follow-up. There were no intervention-related serious adverse events. Mean total HIV DNA at weeks 16 and 18 was 3.02 log10 copies HIV DNA/106 CD4+ T-cells in the control and 3.06 log10 copies HIV DNA/106 CD4+ T-cells in the intervention arm, with no statistically significant difference (mean difference of 0.04 (95%CI -0.03, 0.11) log10 total HIV DNA copies/106 CD4+ T-cells (p=0.26)). Interpretation: This ‘kick-and-kill’ approach conferred no significant benefit compared to ART alone on measures of the HIV reservoir. Although this does not disprove the ‘kick and kill’ strategy, for future ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/299234 |
| DOI: |
10.17863/CAM.46299 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/299234; https://doi.org/10.17863/CAM.46299 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 International ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.4FB90483 |
| Database: |
BASE |